CA2574109A1 - Detection of cell membrane-associated proteins using membrane fragments displayed on encoded microparticle arrays - Google Patents
Detection of cell membrane-associated proteins using membrane fragments displayed on encoded microparticle arrays Download PDFInfo
- Publication number
- CA2574109A1 CA2574109A1 CA002574109A CA2574109A CA2574109A1 CA 2574109 A1 CA2574109 A1 CA 2574109A1 CA 002574109 A CA002574109 A CA 002574109A CA 2574109 A CA2574109 A CA 2574109A CA 2574109 A1 CA2574109 A1 CA 2574109A1
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- microparticles
- labeling agent
- serum
- antibodies
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- 239000012634 fragment Substances 0.000 title claims abstract 18
- 239000012528 membrane Substances 0.000 title claims abstract 15
- 210000000170 cell membrane Anatomy 0.000 title claims abstract 11
- 238000001514 detection method Methods 0.000 title claims abstract 7
- 239000011859 microparticle Substances 0.000 title claims 41
- 102000018697 Membrane Proteins Human genes 0.000 title 1
- 108010052285 Membrane Proteins Proteins 0.000 title 1
- 238000003491 array Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 27
- 210000002966 serum Anatomy 0.000 claims abstract 17
- 210000004027 cell Anatomy 0.000 claims abstract 14
- 239000000427 antigen Substances 0.000 claims abstract 10
- 102000036639 antigens Human genes 0.000 claims abstract 10
- 108091007433 antigens Proteins 0.000 claims abstract 10
- 239000003446 ligand Substances 0.000 claims abstract 6
- 239000003795 chemical substances by application Substances 0.000 claims 20
- 238000002372 labelling Methods 0.000 claims 20
- 238000005286 illumination Methods 0.000 claims 3
- 239000012491 analyte Substances 0.000 claims 2
- 210000000265 leukocyte Anatomy 0.000 claims 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims 1
- 102000004310 Ion Channels Human genes 0.000 claims 1
- 239000011324 bead Substances 0.000 claims 1
- 239000000470 constituent Substances 0.000 claims 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 230000008685 targeting Effects 0.000 claims 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 239000011325 microbead Substances 0.000 abstract 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/5432—Liposomes or microcapsules
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
- G01N33/56972—White blood cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/971—Capture of complex after antigen-antibody reaction
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/110833—Utilizing a moving indicator strip or tape
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Rehabilitation Therapy (AREA)
- Rheumatology (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
Disclosed are methods relating to cell membrane fragments associated with microbeads, so that the characteristics of the cells the fragments originated from can be determined. The fragments can be oriented with what was the outer surface of the cell membrane facing outwardly, so that the antigens associated with the membrane can be contact with ligands (including antibodies) to antigens in the membranes which would be accessible to antibodies in vivo. The system is useful, inter alia, for detection of panel reactive antibodies in donor serum, as well as detection of other cell membrane antigens; or quantitation of particular cell membrane antigens.
Claims (18)
1. A method for the multiplexed detection of membrane-associated receptors, the method comprising:
providing an array of encoded microparticles of distinguishable types, wherein the microparticles display membrane fragments containing membrane-associated antigens, and wherein different membrane fragments which originate from different cell types or from different individuals are displayed on distinguishable types of microparticles;
contacting said array with an analyte solution containing ligands capable of binding to said membrane-associated antigens to form antigen-ligand complexes;
removing said analyte solution;
incubating said array with at least one labeling agent capable of binding to said antigen-ligand complexes;
removing unbound labeling agent;
detecting the presence of labeling agent on microparticles to determine the presence or absence of ligands on said microparticles; and decoding the labeled microparticles in order to determine the type of membrane-associated antigens contained within different membrane fragments displayed on distinguishable microparticle types.
providing an array of encoded microparticles of distinguishable types, wherein the microparticles display membrane fragments containing membrane-associated antigens, and wherein different membrane fragments which originate from different cell types or from different individuals are displayed on distinguishable types of microparticles;
contacting said array with an analyte solution containing ligands capable of binding to said membrane-associated antigens to form antigen-ligand complexes;
removing said analyte solution;
incubating said array with at least one labeling agent capable of binding to said antigen-ligand complexes;
removing unbound labeling agent;
detecting the presence of labeling agent on microparticles to determine the presence or absence of ligands on said microparticles; and decoding the labeled microparticles in order to determine the type of membrane-associated antigens contained within different membrane fragments displayed on distinguishable microparticle types.
2. The method of claim 1 wherein the membrane-associated antigens are one or more of: a G-protein coupled receptor, an ion channel, a class I or class II
human leukocyte antigen, an antibody including an auto-antibody or an allo-antibody or a recombinant antibody or a fragment thereof.
human leukocyte antigen, an antibody including an auto-antibody or an allo-antibody or a recombinant antibody or a fragment thereof.
3. The method of claim 1 wherein there are several types of labeling agents and each type targets a particular type of ligand.
4. The method of claim 1 wherein the labeling agent fluoresces under appropriate illumination.
5. The method of claim 1 wherein the microparticles are distinguished by fluorescence.
6. The method of claim 1 wherein the microparticles are optically encoded.
7. The method of claim 6 wherein the labeling agent is detected and the microparticles are decoded using a microscope.
8. A method for determining the relative amount of panel reactive antibodies in serum, said method comprising:
providing an array of encoded microparticles of distinguishable types, wherein distinguishable types of microparticles display membrane fragments which originate from different cell types or from different individuals and the membrane fragments present a known set of human leukocyte antigens (HLA) molecules;
contacting said set of encoded microparticles with said serum under conditions permitting serum allo-antibodies to bind to HLA so as to form an HLA-antibody complex;
removing serum and its components which do not bind to said HLA
molecules;
incubating said set of microparticles with at least one labeling agent capable of binding to said HLA-antibody complexes;
removing unbound labeling agent;
detecting the presence of labeling agent on microparticles to determine the presence or absence of reactive allo-antibodies on said microparticles;
decoding the labeled microparticles in order to determine the set of HLA
molecules associated with said distinguishable microparticle types; and determining the proportion of microparticles in the array having reactive allo-antibodies.
providing an array of encoded microparticles of distinguishable types, wherein distinguishable types of microparticles display membrane fragments which originate from different cell types or from different individuals and the membrane fragments present a known set of human leukocyte antigens (HLA) molecules;
contacting said set of encoded microparticles with said serum under conditions permitting serum allo-antibodies to bind to HLA so as to form an HLA-antibody complex;
removing serum and its components which do not bind to said HLA
molecules;
incubating said set of microparticles with at least one labeling agent capable of binding to said HLA-antibody complexes;
removing unbound labeling agent;
detecting the presence of labeling agent on microparticles to determine the presence or absence of reactive allo-antibodies on said microparticles;
decoding the labeled microparticles in order to determine the set of HLA
molecules associated with said distinguishable microparticle types; and determining the proportion of microparticles in the array having reactive allo-antibodies.
9. The method of claim 8 wherein the serum is human in origin.
10. The method of claim 8 wherein the labeling agent is an antibody which specifically targets allo-antibodies.
11. The method of claim 10 wherein the labeling agent fluoresces under appropriate illumination.
12. The method of claim 10 wherein the microparticles are decoded based on fluorescence.
13. The method of claim 12 wherein the detection of labeling agent and the decoding can be accomplished using a microscope.
14. A method of affixing cell membrane fragments on the surface of a microparticle whereby, for the majority of the fragments, the outer surface of the membrane faces away from the surface, comprising:
functionalizing the surface with antibodies targeting phosphatidyl serine or phosphatidylethanolamine; and capturing cell membrane fragments with said antibodies.
functionalizing the surface with antibodies targeting phosphatidyl serine or phosphatidylethanolamine; and capturing cell membrane fragments with said antibodies.
15. The method of claim 14 wherein the microparticles are color-encoded and cell membrane fragments originating from different cell types or different individuals are affixed to differently-encoded microparticles.
16. A method of affixing cell membrane fragments to the surface of a microparticle whereby, for the majority of the fragments, the outer surface of the membrane faces away from the surface, comprising:
providing the surface with a positive charge; and capturing cell membrane fragments containing negatively charged constituents.
providing the surface with a positive charge; and capturing cell membrane fragments containing negatively charged constituents.
17. The method of claim 16 wherein the microparticles are color-encoded and cell membrane fragments originating from different cell types or different individuals are affixed to differently-encoded microparticles.
18. A method of multiplexed detection of autoantibodies in serum comprising:
providing a set of encoded microparticles of distinguishable types, wherein each type displays a different autoantigen;
contacting said set of encoded microparticles with said serum under conditions permitting serum auto-antibodies to bind to autoantigens so as to form a complex;
removing said serum components which do not specifically bind to said autoantigens;
incubating said set of microparticles with at least one labeling agent capable of specifically decorating said complexes;
removing unbound labeling agent;
optically detecting the presence of labeling agent on individual microparticles to determine the presence or absence of reactive auto-antibodies in the serum; and decoding the microparticles in order to determine the autoantibody associated with distinguishable microparticle types.
21. The method of claim 20 wherein the serum is human in origin.
22. The method of claim 20 wherein the labeling agent is an antibody which specifically targets auto-antibodies.
23. The method of claim 20 wherein the labeling agent fluoresces under appropriate illumination.
24. The method of claim 23 wherein the beads are distinguished by fluorescence.
25. The method of claim 23 wherein the detection of the label and the decoding can be accomplished using a microscope.
26. A method for determining the presence of anti-T cell or anti-B cell antibodies in the serum of a transfusion or transplant receipient, comprising:
providing a set of encoded microparticles of distinguishable types, wherein each type displays a an anti-T cell or an anti-B cell mononclonal antibody;
contacting said set of encoded microparticles with said serum from a prospective donor under conditions permitting cells to bind to the microparticle-bound antibodies;
contacting said encoded microparticles with the serum from a potential recipient;
removing said serum components which do not specifically bind to said autoantigens;
incubating said set of microparticles with at least one labeling agent capable of specifically decorating antibodies from the recipient which are bound to the cells;
removing unbound labeling agent;
optically detecting the presence of labeling agent on individual microparticles to determine the presence or absence of anti-T cell o'r anti-B
cell antibodies in the serum of the recipient; and decoding the microparticles in order to determine the cells associated with distinguishable microparticle types.
providing a set of encoded microparticles of distinguishable types, wherein each type displays a different autoantigen;
contacting said set of encoded microparticles with said serum under conditions permitting serum auto-antibodies to bind to autoantigens so as to form a complex;
removing said serum components which do not specifically bind to said autoantigens;
incubating said set of microparticles with at least one labeling agent capable of specifically decorating said complexes;
removing unbound labeling agent;
optically detecting the presence of labeling agent on individual microparticles to determine the presence or absence of reactive auto-antibodies in the serum; and decoding the microparticles in order to determine the autoantibody associated with distinguishable microparticle types.
21. The method of claim 20 wherein the serum is human in origin.
22. The method of claim 20 wherein the labeling agent is an antibody which specifically targets auto-antibodies.
23. The method of claim 20 wherein the labeling agent fluoresces under appropriate illumination.
24. The method of claim 23 wherein the beads are distinguished by fluorescence.
25. The method of claim 23 wherein the detection of the label and the decoding can be accomplished using a microscope.
26. A method for determining the presence of anti-T cell or anti-B cell antibodies in the serum of a transfusion or transplant receipient, comprising:
providing a set of encoded microparticles of distinguishable types, wherein each type displays a an anti-T cell or an anti-B cell mononclonal antibody;
contacting said set of encoded microparticles with said serum from a prospective donor under conditions permitting cells to bind to the microparticle-bound antibodies;
contacting said encoded microparticles with the serum from a potential recipient;
removing said serum components which do not specifically bind to said autoantigens;
incubating said set of microparticles with at least one labeling agent capable of specifically decorating antibodies from the recipient which are bound to the cells;
removing unbound labeling agent;
optically detecting the presence of labeling agent on individual microparticles to determine the presence or absence of anti-T cell o'r anti-B
cell antibodies in the serum of the recipient; and decoding the microparticles in order to determine the cells associated with distinguishable microparticle types.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48745203P | 2003-07-15 | 2003-07-15 | |
| US60/487,452 | 2003-07-15 | ||
| PCT/US2004/022782 WO2005006960A2 (en) | 2003-07-15 | 2004-07-15 | Detection of cell membrane-associated proteins using membrane fragments displayed on encoded microparticle arrays |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2574109A1 true CA2574109A1 (en) | 2005-01-27 |
| CA2574109C CA2574109C (en) | 2012-11-13 |
Family
ID=34079372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2574109A Expired - Fee Related CA2574109C (en) | 2003-07-15 | 2004-07-15 | Detection of cell membrane-associated proteins using membrane fragments displayed on encoded microparticle arrays |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US7332349B2 (en) |
| CA (1) | CA2574109C (en) |
| TW (1) | TW200508609A (en) |
| WO (1) | WO2005006960A2 (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2917174B1 (en) * | 2007-06-08 | 2021-02-12 | Bio Rad Pasteur | MULTIPLE ANALYSIS OF BLOOD SAMPLES |
| US8628932B2 (en) | 2007-07-03 | 2014-01-14 | One Lambda | Methods of detecting antibodies specific for denatured HLA antigens |
| WO2009006312A1 (en) * | 2007-07-03 | 2009-01-08 | One Lambda | Methods of detecting antibodies specific for denatured hla antigens |
| NZ584558A (en) * | 2007-09-11 | 2012-10-26 | Kode Biotech Ltd | Peptide-lipid constructs and their use in diagnostic and therapeutic applications |
| WO2009117370A1 (en) * | 2008-03-16 | 2009-09-24 | Synamem Corporation | Membrane-coated particles |
| KR20110036600A (en) | 2008-06-30 | 2011-04-07 | 인썸(인스티튜트 내셔날 드 라 싼테 에 드 라 리셰르셰메디칼르) | Detection of shed cd31, diagnosis of atherothrombosis and autoimmune disorders, and methods for analyzing signaling pathways |
| CA2740192C (en) | 2008-12-01 | 2019-12-31 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for detection of complement fixing antibodies |
| GB0913258D0 (en) | 2009-07-29 | 2009-09-02 | Dynex Technologies Inc | Reagent dispenser |
| US9523701B2 (en) | 2009-07-29 | 2016-12-20 | Dynex Technologies, Inc. | Sample plate systems and methods |
| US20120178081A1 (en) * | 2010-12-31 | 2012-07-12 | Affymetrix. Inc. | Methods of Labeling Cells, Labeled Cells, and uses Thereof |
| US8852873B2 (en) | 2012-04-13 | 2014-10-07 | Diabetomics, Llc | Maternal biomarkers for gestational diabetes |
| AU2014236882B2 (en) * | 2013-03-14 | 2019-01-31 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of detecting donor-specific antibodies and systems for practicing the same |
| US10527613B2 (en) | 2015-11-10 | 2020-01-07 | The Board Of Trustees Of The Leland Stanford Junior University | Biomarker detection methods and systems and kits for practicing same |
| WO2021002650A1 (en) * | 2019-06-30 | 2021-01-07 | 주식회사 알틱스 | Cross-matching image processing method and apparatus based on deep learning |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE366418T1 (en) * | 1996-04-25 | 2007-07-15 | Bioarray Solutions Ltd | LIGHT-REGULATED, ELECTROKINETIC COMPOSITION OF PARTICLES ON SURFACES |
| US5948627A (en) * | 1997-05-30 | 1999-09-07 | One Lambda | Immunobead flow cytometric detection of anti-HLA panel-reactive antibody |
-
2004
- 2004-07-12 TW TW093120755A patent/TW200508609A/en unknown
- 2004-07-15 WO PCT/US2004/022782 patent/WO2005006960A2/en active Application Filing
- 2004-07-15 CA CA2574109A patent/CA2574109C/en not_active Expired - Fee Related
- 2004-07-15 US US10/891,911 patent/US7332349B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20050059095A1 (en) | 2005-03-17 |
| TW200508609A (en) | 2005-03-01 |
| WO2005006960A2 (en) | 2005-01-27 |
| CA2574109C (en) | 2012-11-13 |
| WO2005006960A3 (en) | 2005-06-30 |
| US7332349B2 (en) | 2008-02-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20180716 |